Phase 2/3 Study of TLC590 for Postsurgical Pain Management

A Phase 2/3, Randomized, Double-blind, Comparator- and Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Efficacy of TLC590 for Postsurgical Pain Management Following Inguinal Hernia Repair

A phase 2/3 randomized, double-blind, 2-part, comparator- and placebo-controlled study to assess the safety, pharmacokinetics and efficacy of postsurgical local infiltration in adult subjects following inguinal hernia repair surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Postsurgical Pain Management
• Intervention / Treatment: Drug: TLC590; Drug: Bupivacain; Drug: Ropivacaine; Drug: Normal saline

Detailed Description

This is a phase 2/3 randomized, double-blind, 2-part, comparator- and placebo-controlled study to assess the safety, pharmacokinetics and efficacy of postsurgical local infiltration in adult subjects following inguinal hernia repair surgery. This study includes 2 parts. An unblinded interim analysis will be performed after completion of part 1 (phase 2, approximately 115 subjects to be randomized for 2 different doses of TLC590, bupivacaine, ropivacaine, or placebo), for selecting a TLC590 dose for part 2 (phase 3, approximately 300 subjects to be randomized for TLC590, bupivacaine, or placebo).In this study, 2 doses of TLC590 24.5 mg/mL in inguinal hernia repair will be assessed in an initial phase 2 part before proceeding to a phase 3 pivotal evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 415
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Grace Tsao; Phone Number: +886-2-26557377; Email: grace@tlcbio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female at least 18 years old
• BMI 18-39 kg/m2
• Scheduled to undergo a primary, unilateral Lichtenstein inguinal hernia repair with mesh
• ASA Physical Status Classification of 1, 2 or 3

Exclusion Criteria:

• Clinically significant abnormal clinical laboratory test value
• Clinically significant 12-lead ECG
• History of orthostatic hypotension or syncope
• History of significant renal, hepatic, gastrointestinal, cardiovascular, metabolic, neurologic, psychiatric, or other condition
• History of seizure or currently taking anticonvulsants
• History of hypersensitivity to bupivacaine/ropivacaine, any other amide-type local anesthetic, propofol, oxycodone or morphine (or other opioids)
• History of severe or refractory post-operative nausea or vomiting (PONV)
• Abnormalities of laboratory parameters: HbA1c, platelet, hemoglobin, WBC, serun bilirubin/alanine aminotransferase/aspartate aminotrasferase, serum creatinine, PTT/INR
• Concurrent acute, or chronic painful restrictive/physical condition
• Received opioid therapy for longer than 4 days per week
• Prohibited medication: aspirin and other anti-platelet medication, anticoagulants, class III antiarrhythmic drugs, strong CYP1A2 inhibitors,systemic corticosteroids, NSAID, opioid, bupivacaine or ropivacaine, any investigational product
• History of drug abuse or alcohol abuse
• Positive results on the urine drug screen or alcohol breath test
• History of HIV; active HBV or HCV
• An inguinal hernia repair in the last 3 months or has undergone 3 or more surgeries within 12 months
• Malignancy in the last 2 years
• Documented sleep apnea or on home continuous positive airway pressure treatment (CPAP)
• Personal or family history of malignant hyperthermia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TLC590 490mg; TLC590 490mg (20mL)	Drug: TLC590; TLC590 490mg or 588mg; Other Names: intestigational drug
Experimental: TLC590 588mg; TLC590 588mg (24mL)	Drug: TLC590; TLC590 490mg or 588mg; Other Names: intestigational drug
Active Comparator: Bupivacaine 75mg; Bupivacaine HCl 75mg (30mL)	Drug: Bupivacain; Bupivacaine 75mg; Other Names: active comparator
Active Comparator: Ropivacaine; Ropivacaine HCl 150mg (30mL) (Part 1)	Drug: Ropivacaine; Ropivacaine 150mg; Other Names: active comparator
Placebo Comparator: Normal saline; Normal Saline 0.9% (20mL or 24mL)	Drug: Normal saline; Normal saline 20mL or 24mL; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 - AUC 0-24 of NPRS-M	AUC 0-24 of NPRS-M, evaluated comparing each dose of TLC590 with Placebo	0-24 hours
Part 2 - AUC 0-72 of NPRS-M	AUC 0-72 of NPRS-M, evaluated comparing each dose of TLC590 with Placebo	0-72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC 0-72 of NPRS-M (active comparator)	AUC 0-72 of NPRS-M (TLC590 vs Bupivacaine)	0-72 hours
Proportion of opioid-free subjects through 72 hours (placebo)	Proportion of opioid-free subjects through 72 hours (TLC590 vs. Placebo)	0-72 hours
Proportion of opioid-free subjects through 72 hours (active comparator)	Proportion of opioid-free subjects through 72 hours (TLC590 vs. Bupivacaine)	0-72 hours

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company
• Investigators: Study Director: Terry Tai, PhD, Taiwan Liposome Company

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: December 3, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine; Ropivacaine
• Other Study ID Numbers: TLC590A2003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No